CAR-T Cell Therapy Targeting to CD19 for R/R ALL

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03919240

Collaborator

Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Refractory and relapsed (R/R) acute lymphoblastic leukemia (ALL) patients with active disease always have a dismal outcome. Chimeric antigen receptor (CAR) T-cell therapy targeting to Cluster of Differentiation Antigen 19 (CD19) has been proved as a potent approach to attain remission in B-cell R/R patients. Therefore, the investigators conduct a trial to evaluate the the efficacy and safety of locally producing CAR T cells targeting CD19, and to analyze the outcome of enrolled B-cell ALL patients with active disease or persistent residual disease.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia With Failed Remission	Biological: CAR T-cell therapy	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

CD19-targeting Chimeric Antigen Receptor T-cell Therapy for Patients With Refractory and Relapsed B-cell Acute Lymphoblastic Leukemia

Actual Study Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CAR T-cell therapy Patients enrolled will receive infusion of CD19-targeting CAR T-cells	Biological: CAR T-cell therapy Patients enrolled will receive infusion of CD19-targeting CAR T-cells with a target dose of 5~10×10E6/kg of recipient weight, after the preparative regimen consisted of fludarabin (30mg/m2, day -5 to -3) and cyclophosphamide (300mg/m2, day -5 to -3).

Arm

Intervention/Treatment

Experimental: CAR T-cell therapy

Patients enrolled will receive infusion of CD19-targeting CAR T-cells

Biological: CAR T-cell therapy

Patients enrolled will receive infusion of CD19-targeting CAR T-cells with a target dose of 5~10×10E6/kg of recipient weight, after the preparative regimen consisted of fludarabin (30mg/m2, day -5 to -3) and cyclophosphamide (300mg/m2, day -5 to -3).

Outcome Measures

Primary Outcome Measures

Complete remission [1 month post infusion]
defined as less than 5% blasts in the bone marrow without myelosuppression, no circulating blasts in peripheral blood, and the absence of extramedullary disease, regardless of cell count recovery
Minimal residual disease response [1 month post infusion]
defined as less than 0.01% bone marrow blasts assessed by multiparameter flow cytometry, and absence of genetic aberrants assessed by karyotype analysis or molecular detection
Cytokine release syndrome [1 month post infusion]
grading according to the criteria proposed by Lee, et al (Blood, 2014, 124: 188-195). This grading system ranges from grade 1 (best) to grade 5 (worst), by measuring related symptoms (such as fever, nausea, fatigue, headache, etc.), oxygen requirement, blood pressure and organ toxicity (referred to CTCAE v4.0 grading)

Secondary Outcome Measures

Overall survival [1 year post infusion]
calculating from the day of CAR T-cell infusion to death or the end of follow-up
Leukemia-free survival [1 year post infusion]
calculating from the day of CAR T-cell infusion to death, disease progression or the end of follow-up
Cumulative incidence of relapse [1 year post infusion]
calculating from the day of CAR T-cell infusion to disease progression or the end of follow-up

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed as CD19+ B-cell acute lymphoblastic leukemia;
Fail to achieve remission, or with persistent residual disease after at least 2 cycles of consolidation;
With an estimated survival of higher than 3 months (according to investigator's judgement);
Sufficient organ function: left ventricular ejection fractions≥ 0.5 by echocardiography, creatinine < 1.6 mg/dL, aspartate aminotransferase/aspartate aminotransferase < 3 x upper limit of normal, bilirubin <2.0 mg/dL;
Karnofsky performance status ≥ 60 or ECOG ≤ 2.

Exclusion Criteria:

Intolerant to immunosuppressive chemotherapies;
With active infection or other uncontrolled complications;
With history of seizure;
Active hepatitis B or hepatitis C infection and HIV infection;
Pregnant or lactating women, or patients refusing to take effective contraception measures;
Other contraindications that considered inappropriate to participate in this trial (according to investigator's judgement).